JHU NIMH Center for novel therapeutics for HIV-associated cognitive disorders. HIV-associated neurocognitive disorders (HAND) remain very prevalent, even among aviremic HIV+ individuals who treated with highly active antiretroviral treatments. HIV-related neuroscience research at Johns Hopkins University has focused on this challenging problem, exploring the issue of sustained CNS inflammation as a critical pathogenic mechanism for neurological damage. Despite the tremendous efforts to understand the mechanisms underlying the persistence of HAND, no definitive adjunctive therapeutics have yet entered clinical practice. There is also an unfilled need to develop surrogate markers and more robust and simpler screening instruments for HAND, to allow for earlier detection, for tracking of the course of HAND, and improving the efficiency of clinical trials. Collaborations at Johns Hopkins had been limited by the lack of a central organizing structure for this type of research, and resources to facilitate cross disciplinary and translational research. The JHU NIMH Center has addressed these needs over the past 5 years and has provided a resource to catalyze interdisciplinary research in HIV neuroscience, with the aim of leading to new therapies. The goals of the renewal application of the JHU NIMH Center are to: 1. To facilitate collaborative research in HIV-related neuroscience with the goal of developing a definitive therapy for HIV associated cognitive disorders based on targeting sustained CNS inflammation. 2. To increase resources for HIV-related neuroscience research at JHU and to enhance the productivity of HiV-related neuroscience research locally, nationally and internationally. 3. To encourage high-risk, innovative developmental research in Neuro-AIDS, especially of a cross-disciplinary nature with the specific aim of encouraging investigators (junior or senior) into this field. 4. To use focused medium throughput screening, using in vitro models to identify novel compounds useful for treatment of HIV-associated cognitive dysfunction with the over-arching theme of reducing the sustained CNS inflammation that we believe underlies the development of HAND. 5. To identify and validate surrogate biomarkers based on proteomics and lipomics.